Insecticidal ester enantiomers

ABSTRACT

The (-) (-) diastereoisomers of the α-cyano-3-phenoxybenzyl and α-ethynyl-3-phenoxybenzyl esters of 1-(4-ethoxyphenyl)-, 1-(4-chlorophenyl)-, and 1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid.

This invention relates to new insecticidal compounds, methods ofpreparing these compounds and to new insecticidal compositionscontaining the compounds.

Throughout this specification, where the context permits, the word"insect" is used in its broad common usage and includes spiders, mites,nematodes and other pests which are not classed as insects in the strictbiological sense. Thus the term implies reference not only to thosesmall invertebrate animals belonging mostly to the class Insecta,comprising six-legged, usually winged forms, such as beetles, bugs,flies and the like, but also to other allied classes of arthropods whosemembers are wingless and usually have more than six legs, such asspiders, wood lice and the like, and especially to the order Acaridaewhich includes the mites and ticks. The words "insecticide" and"insecticidal" are similarly used.

The compounds provided by this invention fall within the broad class ofcompounds disclosed in our copending Australian Patent Application No.42723/78. Such compounds have the general formula I ##STR1## wherein R¹is hydrogen or a methoxy, ethoxy, propoxy, butoxy, tetrafluoroethoxy,methylthio, ethylthio, propylthio, fluoro, chloro, bromo, methyl, ethyl,or nitro group, and R² is hydrogen or a methyl group, or R¹ and R²together form a methylenedioxy group;

R³ is hydrogen, or a lower alkyl group, or one of the following groups(a) to (f): ##STR2## and Y¹, Y², Y³, Y⁴, Y⁵ and Y⁶ are the same ordifferent groups and each is hydrogen or a fluoro, bromo or chlorogroup, with the proviso that when R¹ is fluoro, chloro, bromo or methyland R² is hydrogen, then one of Y¹ to Y⁶ is other than hydrogen.

As described in our aforementioned copending application, the compoundsof formula I in which R³ is one of groups (a) to (f) are active asinsecticides, having an insecticidal activity an order of magnitudegreater than most known insecticides. The compounds also possess theproperty of contact repellency to insects.

As also mentioned in our copending Application, the compounds of theformula I above are optically active, the acids (formula I, R³ ═H)having an assymetric carbon atom (C₁ of the cyclobutane ring) and thusare potentially resolvable into optical isomers.

Thus the acid, 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylic acid (formula I, R¹ ═OEt, R² ═R³ ═H, Y¹ to Y⁴ ═F; Y⁵, Y⁶ ═H)was resolved and esterified with 3-phenoxybenzyl alcohol to give theR(-) isomer of the ester (formula I, R¹ ═OEt, R² ═H, R³ ═(a), Y¹ to Y⁴═F; Y⁵, Y⁶ ═H). The latter was shown to have more than twice theactivity of the racemic form of the ester.

Where the alcohol (R³ OH), from which the esters are derived, also hasan assymetric centre, as in the case where R³ is of the groups (c), (e)or (f), the esters are capable of existing in four enantiomeric forms aswell as the racemic forms.

We have now investigated these enantiomeric forms and have found thatthey show surprising differences in insecticidal activity. In general,we have found that of the four possible enantiomers, one is highlyactive, while the others are of low activity. Usually, the level ofactivity of the most active enantiomer is considerably greater, whencompared with the activity of the unresolved compound, than would beexpected if in the unresolved compound, the lower activity enantiomerswere acting simply as inert diluent. In other words, the low activityenantiomers appear to have an inhibitory or antagonistic action on themost active enantioner.

Accordingly, the present invention provides the (-)(-) diastereoisomersof the compounds of the formula I stated above wherein R¹ is ethoxy orchloro and R² is hydrogen; or R¹ and R² together form a methylenedioxygroup; R³ is one of the groups (c) and (e); each of Y¹ to Y⁴ is fluoro;and Y⁵ and Y⁶ are hydrogen. The configurations of the acid and alcoholmoieties are as measured by optical rotation.

The preferred compounds provided by this invention are:

(-)(-)-α-cyano-3'-phenoxybenzyl1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate;

(-)(-)-α-ethynyl-3'-phenoxybenzyl1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate;

(-)(-)-α-ethynyl-3'-phenoxybenzyl1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate;

(-)(-)-α-ethynyl-3'-phenoxybenzyl1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate.

The general methods of preparation of the acids and esters of formula Iare described in our aforesaid copending application. Briefly stated thecompounds I in which R is one of the groups (a) to (f) may be preparedby esterification of the free acid (formula I, R³ ═H) with theappropriate alcohol R³ OH, where R³ is one of the groups (a) to (f).Such esterification may be carried out by any suitable known method,e.g., by direct reaction, or by prior conversion of the acid and/or thealcohol to a suitable reactive derivative, or by an ester interchangereaction between the alcohol R³ OH (R³ ═(a) to (f)) and a lower alkylester of the acid.

The specified diastereoisomers of the present invention may be preparedby first resolving the appropriate acid (formula I, R³ ═H) and/or thealcohol (R³ OH; R³ ═(c) or (e)) to obtain the (-) forms of the acidand/or the alcohol, and forming the ester by the general method juststated, under conditions which do not racemize the resolved component.Where the acid or alcohol is unresolved before esterification, theindividual ester diastereoisomers are separated, after esterification bya suitable method.

Any suitable method can be used for resolution of the startingmaterials. In the case of the acid we have obtained good results byforming the amide with (-)-α-phenylethylamine, separating the respectivediastereoisomers by liquid chromatography and hydrolysing the separatedisomers under mild (non-racemizing) conditions.

Separation of the ester enantiomers, where necessary, afteresterification can be obtained by preparative liquid chromatography(HPLC).

The compounds of the invention show insecticidal activities which aresuperior to the unresolved enantioner mixtures. When used withpotentiators (as described hereinafter) their activities are stillfurther enhanced--to as much as 10 times the potentiated activity of thenext best enantiomer mixture.

The new compounds also show potentiated activity which is superior toknown commercial insecticides of the synthetic pyrethroid type.

The new compounds described herein may be dissolved in a suitableorganic solvent, or mixture of solvents, to form solutions or broughtinto aqueous suspension by dispersing organic solvent solutions of thecompounds in water, to provide useful liquid compositions, which may beincorporated, for example, into aerosol-type dispersions with the usualpropellants.

The compounds may also be incorporated in solid compositions which mayinclude inert solid diluents or carriers, to form useful solidcompositions. Such compositions may also include other substances suchas wetting, dispersing or sticking agents, and may be prepared ingranular or other forms to provide slow release of the compounds over anextended period of time. The compounds may be employed in suchcompositions either as the sole toxic agent or in combination with otherinsecticides such as pyrethrum, rotenone, or with fungicidal orbactericidal agents, to provide compositions useful for household andagricultural dusts and sprays, textile coating and impregnation, and thelike.

In particular, the compounds of the invention may be advantageouslycombined with other substances which have a synergistic or potentiatingaction. Generally such substances are of the class of microsomal oxidaseinhibitors i.e., they inhibit the detoxification of insecticides ininsects produced by the action of oxidative enzymes. Typical substancesof this type are the pyrethrin synergists of which the following areexamples:

    ______________________________________                                        Common Name     Chemical Name                                                 ______________________________________                                        Piperonyl butoxide                                                                            α[2-(2-butoxyethoxy)ethoxy]-                                            4,5-methylenedioxy-2-propyl-                                                  toluene                                                       Piperonyl cyclonene                                                                           3-hexyl-5(3,4-methylenedioxy-                                                 phenyl)-2-cyclohexanone                                       "Sesoxane" (Sesamex)                                                                          2-(3,4-methylenedioxy-phenoxy)-                                               3,6,9-trioxaudecane                                           "Sulfoxide"     1,2-(methylenedioxy)-4-[2-                                                    (octylsulfinyl)propyl]-benz-                                                  ene                                                           n-Propyl isome  dipropyl-5,6,7,8-tetrahydro-                                                  7-methylnaphtho-[2,3-d]-],                                                    3-dioxole-5,6-dicarboxylate                                   ______________________________________                                         ("Sesoxane", "Sesamex" and "Sulfoxide" are Registered Trade Marks).      

Piperonyl butoxide is particularly useful as a potentiator. The amountof piperonyl butoxide used may vary from 1/1000th to five times theweight of the compound I the preferred range being from about 1/100th toan equal part by weight. `Sesoxane` (made by Shulton Inc., Clifton, N.J.U.S.A.) also is a useful potentiator in similar amounts.

The preparation and properties of the compounds of the invention areillustrated by the following specific examples. It should be noted, ofcourse, that these examples are intended to be illustrative of themethods and procedures utilized in preparing the compounds and that theyare not intended to be restrictive or to be regarded as embodying theonly way in which the compounds can be formed and recovered.

EXAMPLE 1 Preparation of Racemic1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid (a)2-(4-ethoxyphenyl)propenoic acid ethyl ester

Alcohol-free sodium ethoxide freshly prepared from sodium (13.9 g) andexcess ethanol was slurried in dry benzene (200 ml.). To this suspensiondiethyl oxalate (88.5 g) was added over 15 minutes.Ethyl-p-ethoxyphenylacetate (114.2 g) was added to the resulting clearyellow solution over 30 minutes at room temperature. After a further 1hour period the reaction mixture solidified. The solid product, sodiumdiethyl-2-p-ethoxyphenyl-3-ethoxy-3-oxido-oxaloacetate was trituratedand washed well with ether. The combined ether washings were evaporatedto a small volume to obtain a second crop of the salt.

The combined yield was 227.4 g.

The sodium salt was acidified by adding it in portions to a well stirredemulsion of equal parts of diethyl ether and dilute acetic acid(approximately 10%). After separation the ether layer was washed withwater and dilute sodium bicarbonate solution, and dried with anhydroussodium sulphate. After evaporation of the ether, the resulting oil wascrystallized from petroleum ether (b.p. 60°-80°), to yield diethyl2-p-ethoxyphenyloxaloacetate 143.8 g (85%), m.p. 59°-60°.

The keto-ester thus obtained (143.8 g) was stirred in diluteformaldehyde solution (62 ml 37% formaldehyde+water 220 ml) and to thesuspension potassium carbonate solution (54.5 g, in water 280 ml) wasadded dropwise. At the end of the addition, ether was added to thestirred suspension to dissolve the gummy precipitate which formed andafter an additional 15 minutes, gas evolution commenced. When this gasevolution ceased (after about 2 hours) the reaction mixture wasextracted with additional ether and the combined ether extracts werewashed with water and evaporated after drying with Na₂ SO₄. The yield ofethyl 2-(4-ethoxyphenyl) propenoate (isolated as a yellow oil) was 97.8g (79.8%).

(b) Ethyl 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate

2-(4-ethoxyphenyl)propenoic acid ethyl ester (13.2 g) was mixed withbenzene (7.5 ml), α-pinene (2 drops) N-ethyldiisopropyl amine (2 drops)and tetrafluoroethylene (15.5 ml) and heated to 150°-155° for 24 hoursthen 155°-60° C. for 17 hours. After evaporation of volatile materialsthe residue (16.6 g) was dissolved in dichloromethane andchromatographed on a column of silica gel to give the ester as acolourless oil 14.5 g (75%). Analysis: C 56.47%, H 5.24%, F 23.4%, C₁₅H₁₆ F₄ O₃ requires C 56.25%, H 5.04%, F. 23.7%.

(c) 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid

Ethyl 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate(14.5 g) was dissolved in ethanol (100 ml) and a 10% w/w solution ofsodium hydroxide in water (100 ml) was added and the mixture refluxedfor 2.5 hours. The mixture was cooled, added to ice water and extractedwith diethyl ether. The aqueous layer was acidified and the precipitatewas filtered off, washed with water, dried and crystallised from 60°-80°petroleum ether to give the acid mp 112°-3° C. Yield 11.2 g (85%).Analysis: C 53.20% H 4.22%, F 25.9%. C₁₃ H₁₂ F₄ O₃ requires C 53.43%, H4.14%, F 26.0%.

EXAMPLE 2 Resolution of1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane Carboxylic Acid (a)Formation and Resolution of diastereoisomeric amides

1-(4-Ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid (5.84g) was converted to the acid chloride by heating on a steam bath with anexcess of thionyl chloride (4.76 g). After the evaporation of excessSOCl₂, the acid chloride, without further purification, was reacted inbenzene (50 ml) with a mixture of pyridine and (-), α-phenethylamine.The mixture of diastereoisomeric amides (7.4 g) was isolated by washingof the solvent layer with dilute HCl and water and evaporation of thesolvent. The respective amide diastereoisomers were separated by liquidchromatography on a silica gel column using n-hexane/ethyl acetate(92/8%) as the eluent, to yield the resolved diastereoisomeric amides ascrystalline solids designated as "A" and "B". A had [α]_(D) ²³ =+37.84°(EtOH), B had [α]_(D) ²³ =-49.56° (EtOH). Yield of A was 2.87 g, m.p.76° C.; B was 1.94 g, m.p., 101° C. IR, mass spectra and NMR of A and Bwere consistent with the amide structure.

(b) Hydrolysis of diastereoisomeric amides

The resolved diastereoisomeric amide A (2.47 g) was added to a solutionof dinitrogen tetroxide (N₂ O₄) 0.15 M in CCl₄ (230 ml) cooled in dryice. The slurried reaction mixture was reacted for 72 h. The reactionmixture was then quenched with ice cold ether (115 ml) and extractedwith NaHCO₃ (5%) and water. The aqueous extract was acidified andextracted with ether. The ether was evaporated and the residual oil ofthe nitrosoamide (3.01 g) refluxed in CCl₄ (50 ml) for 20 hours. TheCCl₄ was then evaporated and the oil reacted for 15 hours withNaOH/methanol (10 ml, 5%) to hydrolyse α-phenethyl carbinol ester formedpartially in the reaction mixture. The phenethyl carbinol was extractedfrom the sodium salt of the resolved acid. The acid recrystallised fromethanol to give 0.85 g of the S(+) enantiomer [α]_(D) ²² =+92.85° (EtOH)of the 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylic acidm.p. 83°-4° C. In a similar experiment the amide B (1.93 g) wasconverted to the R(-) enantiomer [α]_(D) ²⁰ =-94.24° (EtOH); m.p. 82°-3°C.; yield 0.36 g.

EXAMPLE 3 (a) R(-);(±) Diastereoisomer ofα-cyano-3'-phenoxybenzyl-1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate

The R(-) 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylicacid obtained in Example 2 (1.02 g) was stirred with freshly distilledoxalyl chloride and heated on a steam bath. After a slow evolution ofHCl ceased (1 h) the solution was cooled to room temperature. Benzene (1ml) containing a drop of pyridine was added and evolution of gas(CO,CO₂) commenced again. The solution was heated on steam bathcarefully to prevent violent gas evolution. In 10 minutes the gasevolution ceased. The solvents were evaporated and the acyl chloridedissolved in benzene (5 ml) was added to α-cyano-3-phenoxybenzylcarbinol in benzene containing pyridine (0.42 g). The reaction mixturewas stirred at room temperature for 48 hours then the solvent layer waswashed sequentially with dilute HCl, water, NaHCO₃, water and finallydried over anhydrous MgSO₄. The oil obtained after evaporation of thesolvent was chromatographed on silica gel using petroleum ether (60°-80°C.): ethyl acetate as eluents. The two major peaks were separatedtogether to yield 1.7 g of the R(-);(±) diastereoisomer of the titleester as a colourless oil; [α]_(D) ²⁰ =-20.1° (EtOH).

(b) Separation of R(-);(±) and R(-);(-) Diastereoisomers ofα-cyano-3'-phenoxybenzyl1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate

0.9 g of the purified R(-);(±) ester was separated by preparative highpressure liquid chromatography (HPLC) to yield 0.30 g of the R(-);(-)diastereoisomer ([α]_(D) ²⁰ =-38.8°[EtOH]) and 0.31 g of the (R-);(+)diastereoisomer ([α]_(D) ²⁰ =-3.65° [EtOH]) together with an unresolvedintermediate fraction.

EXAMPLE 4 (a) R(-);(±) Diastereoisomer ofα-ethynyl-3'-phenoxybenzyl-1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate

The title compound was prepared from 1.1 g of the R(-)1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid and3-phenoxy-α-ethynylbenzyl carbinol using the method of Example 3(a).Yield of the product was 1.2 g with [α]_(D) ²⁰ =-21.9° (EtOH).

(b) Separation of R(-);(+) and R(-);(-) Diastereoisomers ofα-ethynyl-3'-phenoxybenzyl1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate

0.61 g of the purified R(-);(±) ester was separated by preparative highpressure liquid chromatography (HPLC) to yield 0.27 g of the R(-);(-)diastereoisomer ([α]_(D) ²⁰ =-34.7° [EtOH]) and 0.28 g of the R(-);(+)diastereoisomer ([α]_(D) ²⁰ =-9.64° [EtOH]) together with an unresolvedintermediate fraction.

EXAMPLE 5 R(-) 1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylic acid

The racemic 1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutane carboxylicacid was prepared from ethyl-p-chlorophenylacetate using the method ofExample 1. m.p. 112°-119° C.

The racemic acid was resolved into its R(-) and S(+) isomers using themethod of Example 2.

R(-) isomer [α]_(D) ²⁰ =-107°. (EtOH)

EXAMPLE 6 Separation of (+) and (-) stereoisomers ofα-ethynyl-3-phenoxybenzyl alcohol

(-)-N-α-phenylethylphthalamic acid was prepared from phthalic anhydrideand (-)α-phenylethylamine by the method of Mann and Wastom (J. Chem.Soc., 1947, 510). The ester of this phthalamic acid with racemicα-ethynyl-3-phenoxybenzyl alcohol was prepared by the method of Humanand Mills (J. Chem. Soc., 1949, S77). The individual (-)(+) and (-)(-)ester diastereoisomers were separated by chromatography (HPLC) and thenhydrolysed with a slight excess of alkali to recover the resolvedα-ethynyl-3'-phenoxybenzyl alcohol.

(-) isomer [α]_(D) ²⁰ =-19.0° (EtOH)

(+) isomer [α]_(D) ²⁰ =19.5° (EtOH)

EXAMPLE 7 R(-)(-) Diastereoisomer ofα-ethynyl-3'-phenoxybenzyl-1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate

R(-) 1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid(1.0 g, 3.54 mM) prepared as in Example 5, was refluxed with thionylchloride (1.5 g) for 45 minutes then excess thionyl chloride was removedin vacuo. The residual acyl chloride was dissolved in petroleum ether40°-60° (30 ml) and added over 10 minutes to a stirred mixture of(-)α-ethynyl-3-phenoxybenzyl alcohol (0.87 g, 3.88 mM), pyridine (0.4 g,5 mM) benzene (40 ml) and petroleum ether 40°-60° (30 ml) maintained at15° C. The mixture was stirred an additional 4 hours then washed withice water, sodium bicarbonate solution, dried over sodium sulphate andsolvent removed in vacuo. The residue was chromatographed over silicagel eluting with benzene/petroleum ether (40°-60°) 1:2 to yield theester as a colourless oil 1.47 g 85%. Rotation [α]_(D) ²⁰ =-37.6°(EtOH).

EXAMPLE 8 (R(-)(±) diastereoisomer ofα-ethynyl-3'-phenoxybenzyl-1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate

The R(-)(+) diastereoisomer ofα-ethynyl-3'-phenoxybenzyl-1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate was prepared by esterifyingR(-)1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutane carboxylic acid(prepared as in Example 5) with (+)α-ethyl-3'-phenoxybenzyl alcohol(prepared in Example 6) using the method of Example 7.

The title R(-)(±) diastereoisomer was prepared by mixing equalquantities of the R(-)(-) diastereoisomer prepared in Example 7 and theR(-)(+) diastereoisomer prepared above.

EXAMPLE 9 R(-)(-) diastereoisomer of α-ethynyl-3'-phenoxybenzyl1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate

The R(-) isomer of1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylicacid was prepared using the methods of Examples 1 and 2. It was thenesterified with the (-) isomer of α-ethynyl-3-phenoxybenzyl alcoholusing the method of Example 7.

The title compound had optical rotation [α]_(D) ²⁰ =-59.4°.

EXAMPLE 10 Insecticidal Activity

Insecticidal activity was investigated against blowfly, Lucilia cuprina.The method used was as follows:

(a) The compounds were tested for activity against a dieldrinsusceptible strain (LBB) which had been collected before dieldrin usagein the field.

The test compound was applied in acetone solution, 0.5 μl dispensed witha Drummond micropipette to the dorsum of the thorax of 2-3 day oldfemales. Adult flies were fed on water and sugar-only and maintained at25° C. and 60-70% RH. The mortalities were determined after 24 hours.Moribund flies were regarded as dead. The LD₅₀ values, in terms ofconcentration, were interpolated from a probit/log dose graph using acomputer program.

(b) Potentiation

The compound was also tested on the insects described above inconjunction with the potentiator piperonyl butoxide by pretreating eachinsect with 1 μl of a 2% solution of the potentiator in acetone.

The mortalities were counted at 48 hours after treatment and comparedwith acetone and acetone/potentiator controls.

The LD₅₀ value was determined as described above.

About the same levels of potentiation were obtained when piperonylbutoxide was replaced by an equal amount of `Sesoxane`.

Using the above-described techniques, LD₅₀ values were determined oneach of the diastereoisomers listed in Table 1.

Comparative tests were also carried out on two commercially available,synthetic pyrethroid insecticides, namely

"Permethrin", i.e., the 3'-phenoxybenzyl ester of3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid;

and

"Decamethrin", i.e. the (IR)(3R)cis-form of α-cyano-3'-phenoxybenzylester of 3-(2',2'-dibromovinyl)-2,2-dimethylcyclopropane carboxylicacid.

For ease of comparison the results obtained are expressed in Table 1, interms of a "potency index" given by ##EQU1##

The LD₅₀ for permethrin was determined concurrently with the LD₅₀ forthe test compound.

The configurations of the compounds as stated were assigned on the basisof the measured optical rotations. Absolute configurations where quotedare based on the configuration of a related enantiomer determined byx-ray crystallographic analysis.

                  TABLE 1                                                         ______________________________________                                        Comparison of Insecticidal Activity of Enantiomers                            against Lucilia Cuprina                                                                       Potency Index                                                 Configuration of Compound                                                                       Compound                                                    Acid moiety                                                                            Alcohol moiety                                                                             alone     With synergist                                ______________________________________                                        α-ethynyl-3'-phenoxybenzyl 1-(4-ethoxyphenyl)2,2,3,3-                   tetrafluorocyclobutane-1-carboxylate                                            (±) (±)       170       360                                           R(-)     (±)       320       350                                           R(-)     (-)          1200      4000                                          R(-)     (+)          36        42                                            α-cyano-3'-phenoxybenzyl 1-(4-ethoxyphenyl)-2,2,3,3-                    tetrafluorocyclobutane-1-carboxylate                                            (±) (±)       80        1000                                          R(-)     (±)       112       2200                                          R(-)     (-)          307       20000                                         R(-)     (+)          21        100                                           S(+)     (±)       8         22                                            S(+)     (+)          19        33                                            S(+)     (-)          0.6       3                                             Permethrin            100       100                                           Decamethrin           330       2000                                          α-ethynyl-3'-phenoxybenzyl 1-(4-chlorophenyl)2,2,3,3-                   tetrafluorocyclobutane-1-carboxylate                                            (±) (±)       250       100                                           R(-)     (±)       650       170                                           R(-)     (-)          1200      670                                           α-ethynyl-3'-phenoxybenzyl 1-(3,4-methylenedioxyphenyl)2,2,3,3-         tetrafluorocyclobutane-1-carboxylate                                            (±) (±)       260       280                                           R(-)     (-)          830       500                                           ______________________________________                                    

We claim:
 1. Compounds of the formula Ia ##STR3## characterised in thatR¹ is ethoxy or chloro, and R² is hydrogen;R³ is ##STR4## and thecompounds are in the form of the (-)(-) diastereoisomers. 2.(-)(-)-α-ethynyl-3'-phenoxybenzyl1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate. 3.(-)(-)-α-ethynyl-3'-phenoxybenzyl1-(4-chlorophenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate. 4.Insecticidal compositions, characterised in that they comprise aninsecticidally effective amount of one or more of the compounds statedin claim 1, incorporated in a suitable inert liquid or solid carrier. 5.Insecticidal compositions as claimed in claim 4, characterised in thatthey additionally contain at least one synergistic or potentiating agentof the class of microsomal oxidase inhibitors which is a pyrethrinsynergist.
 6. Insecticidal compositions as claimed in claim 5,characterised in that the synergist is one of thefollowing:α[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene;3-hexyl-5(3,4-methylenedioxyphenyl)-2-cyclohexanone;2-(3,4-methylenedioxy-phenoxy)-3,6,9-trioxaundecane;1,2-(methylenedioxy)-4-[2-octylsulfinyl)propyl]-benzene;dipropyl-5,6,7,8-tetrahydro-7-methylnaphtho-[2,3-d]-1,3-dioxole-5,6-dicarboxylate.7. Insecticidal compositions as claimed in claim 5, characterised inthat the synergist is used in an amount from about 1/1000th to 5 timesthe weight of the compound I.
 8. Insecticidal compositions as claimed inclaim 5, characterised in that the synthergist is used in an amount fromabout 1/100th to an equal part by weight per part of the compound I. 9.A method of combatting insect pests, characterised in that aninsecticidally effective amount of a compound or composition as claimedin any one of claims 1 to 3 or 4 to 8, is applied to the insects and/ortheir locus.